A successfully treated case of hypopituitarism complicated with hyperosmolar hyperglycaemic state and rhabdomyolysis

Introduction

Hypopituitarism is a clinical syndrome in which there is a deficiency in hormone production by the pituitary gland. The condition often leads to hypoglycaemia. Here, we report a case of a 23-year-old Chinese male who was admitted to our hospital in a hyperosmolar hyperglycaemic state (HHS) combined with hypopituitarism and rhabdomyolysis. HHS sometimes induces rhabdomyolysis and temporal acute kidney injury. The mortality rate of HHS ranges from 10% to 50% ¹ due to the high incidence of coexisting disease. Age (>65 years), degree of hyperosmolarity (>375 mOsm/L), ² hemodynamic instability, ³ a low Glasgow coma scale score on admission and precipitation by infection ⁴ are powerful predictors of a fatal outcome.

Rhabdomyolysis is defined as a clinical and laboratory syndrome resulting from skeletal muscle injury with release of muscle cell contents into the plasma. Apart from crush injuries, various non-traumatic causes may also be implicated such as alcohol, drug overdose, hypokalaemia, hypophosphataemia and hypothermia. Therefore, it is crucial to establish a timely diagnosis and standardised treatments.

Case presentation

A 23-year-old Chinese man was admitted to our hospital because of drowsiness. Two months prior, he had undergone surgery to remove a germinoma located in the sella region. He also received Gamma-knife radio-surgery after another month. During the previous two weeks, he had suffered general fatigue and anorexia. He took dexamethasone (3 mg) for a day as treatment, but his symptoms did not change. After two days, the symptoms became more serious, and he could not move due to lower limb muscle pain and weakness. Five hours before his admission, he became drowsy. On admission, his blood pressure was 130/80 mmHg, his pulse rate was 102 beats/min, his respiratory rate was 33/min and his body temperature was 37.1℃. An oropharyngeal examination revealed an extremely dry oral mucosa. A chest and abdominal examination revealed no abnormalities. Muscle strength of the upper limbs was grade 3, and that of the lower limbs was grade 0. The pathologic reflex was not drawn out. Blood tests revealed severe hyperglycaemia, electrolyte abnormalities, elevated myoglobin, leukocytosis (Table 1) and hypopituitarism (Figure 1). His calculated plasma osmolarity was 427 mOsm/L.

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Table 1.

Laboratory findings on admission.

Peripheral blood		Blood chemistry		Urinalysis
White blood cell	10,290/µL	AST	180.00 IU/L	Gravity	1.005
		ALT	95.00 IU/L	pH	5.50
		LDH	270.00 IU/L	Protein	1+
Red blood cells	541 × 104/µL	Total protein	6.40 g/dL	Occult blood	3+
Haemoglobin	14.8 g/dL	Albumin	4.09 g/dL	Sugar	4+
		Blood urea nitrogen	28.01 mg/dL	Ketones	(−)
Platelets	11.3 × 104/µL			Red blood cells 4.40/hpf	4.40/hpf
Coagulation		Creatinine	1.02 mg/dL	Serological test
PT	13 s	Glucose	574.67 mg/dL	HbA1c	9.60%
APTT	36 s	Myoglobin	>3000 ng/mL	Arterial blood gas
Fibrinogen	334 mg/dl	Sodium	189.00 mEq/L	pH	7.44
PT-INR	1.01	Potassium	3.50 mEq/L	PO2	72.00 mmHg
TT	18 s	Chloride	141.08 mEq/L	pCO2	45.00 mmHg
PTA	99%	Calcium	4.46 mEq/L	HCO3−	30.60 mmol/L
Urine ions				Base excess	5.20 mmol/L
24 h K	38.67 mmol/24 h
24 h Na	9.80 mmol/24 h
24 h Ca	1.19 mmol/24 h

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Figure 1.

Function of pituitary-target gland axis. Diagram shows the regulation of thyroid, adrenocorticoids and sex hormones in the patient. Downward arrows indicate down-regulation of the hormones. Numbers in parentheses indicate normal ranges of hormone concentrations. TSH, ACTH, LH and FSH are secreted from anterior pituitary gland.

On admission, hypopituitarism, HHS and rhabdomyolysis were diagnosed. After fluid resuscitation (0.9% NaCl) and insulin infusion, the patient’s blood sugar levels gradually decreased. By the second day of hospitalisation, his blood sugar levels had decreased from 574 mmol/L to 196 mmol/L, his osmolarity decreased from 427 to 355 mOsm/L and his consciousness was restored; however, his muscle strength had not improved. His myoglobin levels were still over 3000 ng/mL (Figure 2). On the third day of hospitalisation, his muscle strength improved (the upper limbs were grade 5 and the lower limbs were grade 2), he stopped complaining of any muscle pain and osmolarity decreased to normal (314 mOsm/L). On the eighth day of hospitalisation, his muscle strength was restored to normal, and his myoglobin levels decreased to 226.1 ng/mL. He could walk unaided, but his appetite was still altered. After a day of administering hydrocortisone (10 mg) replacement therapy, on the 10th day of hospitalisation his appetite was remarkably increased and he was discharged. OPEN IN VIEWER

Discussion

Hypopituitarism is a clinical syndrome in which there is a deficiency in hormone production by the pituitary. This may result from disorders involving the pituitary gland, hypothalamus or surrounding structures. In this case, surgery and radio-surgery treatment led to hypopituitarism. In previous cases wherein patients with diabetes mellitus experienced complications of hypopituitarism, they required little or no insulin and frequently exhibited normal or low levels of glucose even without insulin treatment, known as the Houssay phenomenon. ⁵ In this case, the patient had HHS, a very rare medical condition, with many potential causes. First, the man had taken too much dexamethasone over the previous two weeks, which might have caused hyperglycaemia. Second, he had polyuria at a level of over 3000 mL per day. The initiating event in HHS is glycosuria diuresis. Glycosuria impairs the concentrating capacity of the kidneys, further exacerbating water loss. Under normal conditions, the kidneys act as a safety valve to eliminate glucose above a certain threshold and prevent further accumulation. However, decreased intravascular volume or underlying renal disease decreases the glomerular filtration rate, causing the glucose level to increase. The loss of more water than sodium leads to hyperosmolarity. Moreover, because the gravity of his urine was less than 1.005, he might have had complications from diabetes insipidus. Third, it is believed that diabetes complicated with hypopituitarism and its symptoms is aggravated by insulin resistance. The Livingstone group reported that there are interactions between sex steroids and insulin in tissues. At physiological levels, testosterone and oestradiol are thought to be involved in maintaining normal insulin sensitivity. ⁶

Rhabdomyolysis may be defined as a clinical and laboratory syndrome resulting from skeletal muscle injury with release of muscle cell contents into the plasma. Apart from crush injuries, various non-traumatic causes may also be implicated such as alcohol, drug overdose, hypokalaemia, hypophosphataemia and hypothermia. ⁷ HHS is a rare cause of rhabdomyolysis. The exact mechanism of rhabdomyolysis in HHS remains unclear. The electrogenic sodium pump is inhibited by HHS, acidosis, hypernatremia and potassium deficiency, as well as by decrease in intramuscular energy supply due to insulin deficiency. This results in a fall in the transmembrane potential, thereby contributing to the development of rhabdomyolysis. ⁸ Hyperosmolar states may also elevate the intracellular calcium concentration. A persistently high intracellular calcium level may bring about the activation of neutral proteases and subsequent leakage of muscle enzymes.

Singhal et al. ⁹ concluded that serum sodium, serum osmolarity and blood glucose are the major determinants for the occurrence of rhabdomyolysis in the diabetic state. According to Gabow et al., ¹⁰ hypokalaemia and hypophosphataemia are important predisposing factors for rhabdomyolysis.

In conclusion, we can say that it is very important to make a timely diagnosis of HHS for a patient who has hypopituitarism, and to initiate the standardised treatments for hypopituitarism and HHS. Our report provides useful indications for the treatment of the disease.